Distribution characteristics of drug resistance mutations of HIV CRF01_AE, CRF07_BC and CRF08_BC from patients under ART in Ganzhou, China.

BACKGROUND: Drug resistance mutation (DRM)-associated virological failure has become a critical issue for ART and the elimination of HIV. OBJECTIVES: To investigate the distribution characteristics of DRMs of HIV CRF01_AE, CRF07_BC and CRF08_BC, the predominant subtypes in China. METHODS: Patients receiving ART up to 31 August 2020 in Ganzhou in China were recruited. Full-length sequences of the HIV pol gene were amplified from patients with virological failure. DRMs and antiretroviral susceptibility were explored using the Stanford University HIV Drug Resistance Database HIVdb Program. RESULTS: Overall, 279 of 2204 patients under ART were found to have virological failure. Nine HIV subtypes were identified among 211 sequences that were amplified successfully and CRF08_BC (37.0%), CRF01_AE (26.1%) and CRF07_BC (25.6%) were the most prevalent, with mutation frequencies of 44.9% (35/78), 52.7% (29/55) and 35.2% (19/54), respectively. The most common DRMs of these three subtypes were K103N and M184V, while the mutation frequencies of M41L, D67N, K70R, K101E, V106M, Y181C, K219E, H221Y and N348I were obviously different among subtypes. The resistance levels and frequencies for antiretroviral drugs for these three subtypes were similar and resistances to nevirapine, efavirenz, lamivudine and emtricitabine were the most frequently observed. Compared with CRF01_AE and CRF07_BC, CRF08_BC had higher proportions of DRMs for NRTIs and lower frequencies of resistance to NRTIs and NNRTIs. CONCLUSIONS: The distribution characteristics of DRMs of HIV CRF01_AE, CRF07_BC and CRF08_BC were inconsistent and should be considered when selecting antiretroviral strategies, developing new drugs and controlling HIV strains containing DRMs.

Temporal changes in laboratory markers of survivors and non-survivors of adult inpatients with COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2, and outbreaks have occurred worldwide. Laboratory test results are an important basis for clinicians to determine patient condition and formulate treatment plans. METHODS: Fifty-two thousand six hundred forty-four laboratory test results with continuous values of adult inpatients who were diagnosed with COVID-19 and hospitalized in the Fifth Hospital in Wuhan between 16 January 2020 and 18 March 2020 were compiled. The first and last test results were compared between survivors and non-survivors with variance test or Welch test. Laboratory test variables with significant differences were then included in the temporal change analysis. RESULTS: Among 94 laboratory test variables in 82 survivors and 25 non-survivors with COVID-19, white blood cell count, neutrophil count/percentage, mean platelet volume, platelet distribution width, platelet-large cell percentage, hypersensitive C-reactive protein, procalcitonin, D-dimer, fibrin (ogen) degradation product, middle fluorescent reticulocyte percentage, immature reticulocyte fraction, lactate dehydrogenase were significantly increased (P < 0.05), and lymphocyte count/percentage, monocyte percentage, eosinophil percentage, prothrombin activity, low fluorescent reticulocyte percentage, plasma carbon dioxide, total calcium, prealbumin, total protein, albumin, albumin-globulin ratio, cholinesterase, total cholesterol, nonhigh-density/low-density/small-dense-low-density lipoprotein cholesterol were significantly decreased in non-survivors compared with survivors (P < 0.05), in both first and last tests. Prothrombin time, prothrombin international normalized ratio, nucleated red blood cell count/percentage, high fluorescent reticulocyte percentage, plasma uric acid, plasma urea nitrogen, cystatin C, sodium, phosphorus, magnesium, myoglobin, creatine kinase (isoenzymes), aspartate aminotransferase, alkaline phosphatase, glucose, triglyceride were significantly increased (P < 0.05), and eosinophil count, basophil percentage, platelet count, thrombocytocrit, antithrombin III, red blood cell count, haemoglobin, haematocrit, total carbon dioxide, acidity-basicity, actual bicarbonate radical, base excess in the extracellular fluid compartment, estimated glomerular filtration rate, high-density lipoprotein cholesterol, apolipoprotein A1/ B were significantly decreased in non-survivors compared with survivors (P < 0.05), only in the last tests. Temporal changes in 26 variables, such as lymphocyte count/percentage, neutrophil count/percentage, and platelet count, were obviously different between survivors and non-survivors. CONCLUSIONS: By the comprehensive usage of the laboratory markers with different temporal changes, patients with a high risk of COVID-19-associated death or progression from mild to severe disease might be identified, allowing for timely targeted treatment.

Genetic Characterization of a Novel HIV-1 Second-Generation Recombinant Form Originating from CRF86_BC and a Unique Recombinant Form in Yunnan, China.

Yunnan is the first place where human immunodeficiency virus type 1 (HIV-1) became prevalent in China, and it is also the place with the most complicated HIV-1 genetic diversity in China. On October 23, 2019, a patient newly diagnosed with acquired immunodeficiency syndrome from a hospital in Baoshan, Yunnan, was recruited for genetic analysis. Near full-length genome of HIV-1 was amplified from the plasma sample. Phylogenetic analysis revealed that this sequence (BS6F24) has a close relationship with CRF86_BC and a unique recombinant form (URF) (KY406739), which was formed by recombination of subtypes B and C. Bootscan analysis confirmed that the first part (HXB2:1022-5832) and last part (HXB2:5833-9120) genomes of BS6F24 had the same recombinant structures as KY406739 and CRF86_BC, respectively. A second-generation recombinant form that originated from CRF86_BC and a URF were reported for the first time. This indicates the need for continuous monitoring of the genetic diversity of HIV-1 in Yunnan, China.

Genetic Characteristics of Three Unique Recombinant Forms of HIV-1 in Yunnan, China.

To explore the molecular epidemiological status of human immunodeficiency virus type 1 (HIV-1) in Yunnan, China, three HIV-1 near full-length genomes were amplified and sequenced from plasma samples that were collected from Burmese patients newly diagnosed with HIV-1 in Dehong Prefecture in Yunnan Province in 2017. Phylogenetic and bootscanning analyses revealed that all the sequences might be HIV-1 second-generation recombinant forms of circulating recombinant forms (CRF07_BC and CRF83_cpx) and unique recombinant forms. One of the sequences contained six CRF01_AE fragments, five subtype C fragments, and two subtype B fragments, which were separated by 12 breakpoints. These results revealed that the second-generation recombination of HIV-1 within different strains is still ongoing in Dehong, China. Systematic surveys and immediate interventions are urgently needed to prevent the formation of increasingly complex HIV-1 recombinant forms.

Genetic Characterization of a Novel HIV-1 Second-Generation Recombinant Form (CRF01_AE/CRF07_BC) Identified in Yan'an City, China.

Owing to co-epidemic of CRF01_AE and CRF07_BC in China, increasing numbers of the second-generation recombinants between them have been identified especially among sexual population. In this study, we identified a unique CRF01_AE/CRF07_BC recombinants from a male HIV-1 positive individual (18YA004) infected by heterosexual contact in Yan'an city, Shaanxi province. The near full-length genome analyses showed 18YA004 was divided into six fragments by five breakpoints located in the pol, vpr, vpu, and nef gene, respectively. Three CRF01_AE segments (segments I, III, and V) were all clustered within the cluster 4a lineage, exclusively circulating among MSM in the northern China. Coupled with our previous finding of CRF01_AE/C recombinant in Yan'an city, the emergence of CRF01_AE/CRF07_BC strain further suggested coexistence of multiple HIV-1 genotypes here. Therefore, it is necessary to continue monitoring the molecular epidemiology of HIV-1 among high-risk groups to obtain a better understanding of the genetic complexity and transmission of HIV-1 in this region.

The Genetic Diversity of HIV-1 Within Antiretroviral-Naive Outpatients in Ganzhou, China.

To explore the molecular epidemiological status of human immunodeficiency virus type 1 (HIV-1) in Ganzhou, China, eight HIV-1-positive outpatients were recruited from July 5 to 21, 2018. Six HIV-1 near-full-length sequences were amplified and sequenced from the plasma samples that were collected before the patients' antiretroviral treatments. Phylogenetic and bootscan analyses revealed that one of the sequences was CRF01_AE, one was CRF55_01B, and two were CRF07_BC. Notably, one of the sequences was a unique recombinant form, and one of them was a second-generation recombinant form of CRF07_BC and subtype C. These results revealed that multiple HIV-1 subtypes are circulating in Ganzhou, China. Systematic surveys with large sample sizes are urgently needed to explore the exact molecular epidemiological characteristics and to trace the origins of HIV-1 in Ganzhou, China.

Identification of a Novel HIV-1 Unique CRF01_AE/C Recombinant in Yan'an City, Shaanxi Province.

A wide variety of HIV-1 recombinants are constantly discovered in China. Comprehensively monitoring the genetic diversity of HIV-1 is very essential for understanding the molecular epidemiology and controlling the spread of the HIV-1 epidemic. In this study, we presented a novel HIV-1 unique CRF01_AE/C recombinant (19YA001) isolated from a female patient infected HIV-1 through heterosexual transmission in Yan'an city, Shaanxi province. The near full-length genome analyses showed 19YA001 was divided into two CRF01_AE and one C segments by two breakpoints observed in the vif/vpr region. To date, this is the first report revealing the characteristic of HIV-1 subtype in Yan'an city. And this unique recombinant strain might imply that the genetic diversity of HIV-1 in Yan'an city is complex. However, the sample size is too small. Further larger studies of HIV-1 molecular epidemiology are urgently needed to provide a better understanding of HIV-1 diversity and transmission in this region.